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59234-48-9

CIS-PIPERIDINE-2,6-DICARBOXYLIC ACID DIMETHYL ESTER HCL synthesis

3synthesis methods
-

Yield:59234-48-9 692 mg

Reaction Conditions:

with thionyl chloride at 0 - 20;

Steps:

cis-meso-N-Benzoyl-teneraic Acid Dimethyl Ester (Dimethyl cis-meso-N-Benzoyl-piperidine-2.6-dicarboxylate, 19c)

Specifically, cis-meso-teneraic acid (3) (1.0 g,5.78 mmol) was added to a stirring solution of thionyl chloride (3.0 mL, 42.0 mmol) in MeOH (30 mL) at 0°C. The mixturewas stirred for 30 min at 0°C, then warmed to room temperature, and was stirred overnight. The solvent was evaporated in vacuo to yield crude cis-meso-teneraic acid dimethylester·HCl (692 mg, 2.92 mmol, 51.0%) that is used in the nextstep without further purification; IR (KBr): 1750 (cm-1).Additionally, Et3N (0.44 mL, 3.20 mmol) and benzoyl chloride (0.20 mL, 1.76 mmol) were added to a solution of the forementioned crude cis-meso-teneraic acid dimethyl ester·HCl(380 mg, 1.60 mmol) in tetrahydrofuran (8.0 mL) at 0°C. Thereaction mixture was stirred overnight at room temperature.The solvent was evaporated in vacuo, and the residue waspartitioned between water (10 mL) and EtOAc (30 mL). Theaqueous phase was further extracted with EtOAc (30 mL). Thecombined organic layers were washed with water (30 mL),aqueous citric acid (10%, 30 mL), and brine (30 mL) and subsequently dried over anhydrous MgSO4 and then concentrated.The crude residue was purified by silica gel column chromatography (eluted with n-hexane-AcOEt) to obtain cis-meso-Nbenzoyl-teneraic acid dimethyl ester (19c) as a viscous oil(250 mg, 8.20 mmol, 51.0%).

References:

Amino, Yusuke;Nishi, Seiichi;Izawa, Kunisuke [Chemical and Pharmaceutical Bulletin,2017,vol. 65,# 9,p. 854 - 861]

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